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Gene Information
Gene symbol: GPBAR1
Gene name: G protein-coupled bile acid receptor 1
HGNC ID: 19680
Synonyms: BG37, GPCR, TGR5, M-BAR, GPCR19, GPR131, MGC40597
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 9575840 | Thus far, two CCK receptors have been molecularly identified to mediate the actions of CCK and gastrin, CCK-A and CCK-B receptors (CCK-AR and CCK-BR, respectively). |
| 2 | 9575840 | The regulation of CCK-AR and CCK-BR affinity by guanine nucleotides and the receptor activation of G protein-dependent stimulation of phospholipase C and adenylyl cyclase suggested that they were guanine nucleotide-binding protein-coupled receptors [G protein-coupled receptors (GPCRs)]; however, the eventual cloning of their cDNAs revealed their heptahelical structure and confirmed their membership in the GPCR superfamily. |
| 3 | 11857909 | Mutations in GPCRs have been associated with dwarfism, congenital hyperthyroidism or hypothyroidism, nephrogenic diabetes insipidus, obesity, resistance to TSH, LH, FSH and ACTH, Jansen's metaphyseal and Blomstrand's chondrodysplasia, autosomal dominant hypoparathyroidism, and neonatal severe hyperparathyroidism. |
| 4 | 11857909 | Mutations in other families of receptors which are characterized into one spanning-transmembrane receptor can result in resistance to insulin, GH, leptin and AMH. |
| 5 | 12356298 | Recently, we have shown that a molecular determinant for nephrogenic diabetes insipidus, the vasopressin receptor with a substitution at the DRY motif arginine (V2R R137H), is a constitutively desensitized receptor that is unable to couple to G proteins due to its constitutive association with beta-arrestin [Barak, L. |
| 6 | 12356298 | In this study, we asked whether the constitutively desensitized phenotype observed in the V2R R137H represents a general paradigm that may be extended to other GPCRs. |
| 7 | 12356298 | We show that arginine substitutions in the DRY motifs of the alpha(1B) adrenergic receptor (alpha(1B)-AR) and angiotensin II type 1A receptor (AT(1A)R) result in receptors that are uncoupled from G proteins, associated with beta-arrestins, and found localized in endocytic vesicles rather than at the plasma membrane in the absence of agonists. |
| 8 | 12491536 | The effects of glucagon are mediated by the glucagon receptor, which is itself a prototypical member of a distinct category called family B receptors within the G protein-coupled superfamily of seven-helical transmembrane receptors (GPCRs). |
| 9 | 12491536 | Information about the glucagon receptor is presented within the context of what is known about other members of the family B GPCRs. |
| 10 | 12491536 | The effects of glucagon are mediated by the glucagon receptor, which is itself a prototypical member of a distinct category called family B receptors within the G protein-coupled superfamily of seven-helical transmembrane receptors (GPCRs). |
| 11 | 12491536 | Information about the glucagon receptor is presented within the context of what is known about other members of the family B GPCRs. |
| 12 | 12750375 | The M3 muscarinic receptor is a prototypical member of the class I family of G protein-coupled receptors (GPCRs). |
| 13 | 14529486 | GLP-1 binds with high affinity to G protein-coupled receptors (GPCRs) located on pancreatic beta-cells, and it exerts insulinotropic actions that include the stimulation of insulin gene transcription, insulin biosynthesis, and insulin secretion. |
| 14 | 14529486 | GLP-1 belongs to a large family of structurally-related hormones and neuropeptides that include glucagon, secretin, GIP, PACAP, and VIP. |
| 15 | 14529486 | Additional modifications of GLP-1 incorporate fatty acylation and drug affinity complex (DAC) technology to improve serum albumin binding, thereby slowing renal clearance of the peptides. |
| 16 | 14529486 | This review summarizes structural features and signal transduction properties of GLP-1 and its cognate beta-cell GPCR. |
| 17 | 14529486 | GLP-1 binds with high affinity to G protein-coupled receptors (GPCRs) located on pancreatic beta-cells, and it exerts insulinotropic actions that include the stimulation of insulin gene transcription, insulin biosynthesis, and insulin secretion. |
| 18 | 14529486 | GLP-1 belongs to a large family of structurally-related hormones and neuropeptides that include glucagon, secretin, GIP, PACAP, and VIP. |
| 19 | 14529486 | Additional modifications of GLP-1 incorporate fatty acylation and drug affinity complex (DAC) technology to improve serum albumin binding, thereby slowing renal clearance of the peptides. |
| 20 | 14529486 | This review summarizes structural features and signal transduction properties of GLP-1 and its cognate beta-cell GPCR. |
| 21 | 14972085 | Membrane receptors that couple to guanine nucleotide binding protein (GPCRs) represent one of the largest families of proteins in the genome. |
| 22 | 15556674 | Mutations in GPCR can cause acquired and inherited diseases such as retinitis pigmentosa (RP), hypo- and hyperthyroidism, nephrogenic diabetes insipidus, several fertility disorders, and even carcinomas. |
| 23 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 24 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 25 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 26 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 27 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 28 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 29 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 30 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 31 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 32 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 33 | 15817468 | The glucagon-like peptide-2 receptor (GLP-2R) is a member of the Family B glucagon-secretin GPCR family, which exhibit significant sequence and structural differences from the Family A receptors in their intracellular and extracellular domains. |
| 34 | 15817468 | However, progressive truncation of the C terminus reduced cell surface receptor expression, altered agonist-induced GLP-2R trafficking, and abrogated protein kinase A-mediated heterologous receptor desensitization. |
| 35 | 15817468 | Taken together with the previously demonstrated clathrin and dynamin-independent, lipid-raft-dependent pathways for internalization, our data suggest that GLP-2 receptor signaling has evolved unique structural and functional mechanisms for control of receptor trafficking, desensitization, and resensitization. |
| 36 | 16185843 | The scaffolding/adapter protein, Gab1, is a key signaling molecule for numerous stimuli including growth factors and G protein-coupled-receptors (GPCRs). |
| 37 | 16185843 | HGF and EGF stimulated total Gab1 tyrosine phosphorylation (TyrP) and TyrP of Gab1 phospho-specific sites (Y307, Y627), but not other pancreatic growth factors, GI GPCRs (CCK, bombesin, carbachol, VIP, secretin), or agents directly activating PKC or increasing Ca2+. |
| 38 | 16185843 | HGF-stimulated Y307 Gab1 TyrP differed in kinetics from total and Y627. |
| 39 | 16185843 | In unstimulated cells>95% of Gab1 was cytosolic and HGF stimulated a 3-fold increase in membrane Gab1. |
| 40 | 16185843 | HGF stimulated equal increases in pY307 and pY627 Gab1 in cytosol/membrane. |
| 41 | 16185843 | HGF stimulated Gab1 association with c-Met, Grb2, SHP2, PI3K, Shc, Crk isoforms and CrkL, but not with PLCgamma1. |
| 42 | 16185843 | These results demonstrate that only a subset of pancreatic growth factors (HGF/EGF) stimulates Gab1 signaling and no pancreatic hormones/neurotransmitters. |
| 43 | 16185843 | The scaffolding/adapter protein, Gab1, is a key signaling molecule for numerous stimuli including growth factors and G protein-coupled-receptors (GPCRs). |
| 44 | 16185843 | HGF and EGF stimulated total Gab1 tyrosine phosphorylation (TyrP) and TyrP of Gab1 phospho-specific sites (Y307, Y627), but not other pancreatic growth factors, GI GPCRs (CCK, bombesin, carbachol, VIP, secretin), or agents directly activating PKC or increasing Ca2+. |
| 45 | 16185843 | HGF-stimulated Y307 Gab1 TyrP differed in kinetics from total and Y627. |
| 46 | 16185843 | In unstimulated cells>95% of Gab1 was cytosolic and HGF stimulated a 3-fold increase in membrane Gab1. |
| 47 | 16185843 | HGF stimulated equal increases in pY307 and pY627 Gab1 in cytosol/membrane. |
| 48 | 16185843 | HGF stimulated Gab1 association with c-Met, Grb2, SHP2, PI3K, Shc, Crk isoforms and CrkL, but not with PLCgamma1. |
| 49 | 16185843 | These results demonstrate that only a subset of pancreatic growth factors (HGF/EGF) stimulates Gab1 signaling and no pancreatic hormones/neurotransmitters. |
| 50 | 16389067 | Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G protein-coupled receptors HM74A and HM74. |
| 51 | 16389067 | Recently, two G protein-coupled receptors (GPCRs) for niacin were identified and characterized as high (HM74A; GPR109A) and low (HM74; GPR109B) affinity receptors based on the binding affinities of niacin. |
| 52 | 16389067 | Constructs expressing HM74A or HM74 were stably transfected into CHO-K1 cells and shown to elicit phosphorylation of p42 and p44 mitogen-activated protein kinase (ERK1/ERK2) phosphorylation upon addition of niacin or acifran. |
| 53 | 16389067 | The presence of functionally coupled GPCRs was further confirmed using Pertussis toxin, which completely inhibited the ability of either niacin or acifran to elicit phospho-ERK1/ERK2. |
| 54 | 16389067 | Two chemical analogs of acifran demonstrated robust phosphorylation of ERK1/ERK2. |
| 55 | 16389067 | Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G protein-coupled receptors HM74A and HM74. |
| 56 | 16389067 | Recently, two G protein-coupled receptors (GPCRs) for niacin were identified and characterized as high (HM74A; GPR109A) and low (HM74; GPR109B) affinity receptors based on the binding affinities of niacin. |
| 57 | 16389067 | Constructs expressing HM74A or HM74 were stably transfected into CHO-K1 cells and shown to elicit phosphorylation of p42 and p44 mitogen-activated protein kinase (ERK1/ERK2) phosphorylation upon addition of niacin or acifran. |
| 58 | 16389067 | The presence of functionally coupled GPCRs was further confirmed using Pertussis toxin, which completely inhibited the ability of either niacin or acifran to elicit phospho-ERK1/ERK2. |
| 59 | 16389067 | Two chemical analogs of acifran demonstrated robust phosphorylation of ERK1/ERK2. |
| 60 | 16541101 | BAs activate mitogen-activated protein kinase pathways, are ligands for the G-protein-coupled receptor TGR5, and activate nuclear hormone receptors such as farnesoid X receptor alpha. |
| 61 | 17123625 | Thyrotropin-releasing hormone (TRH), a tripeptide, exerts its biological effects through stimulation of cell-surface receptors, TRH-R, belonging to the superfamily of G protein-coupled receptors (GPCR). |
| 62 | 17123625 | Because of the intermediate size of TRH, it is smaller than polypeptide ligands that interact at GPCR ectodomains and larger than biogenic amines, which interact within GPCR transmembrane domains (TMD), the TRH/TRH-R complex probably shares properties of these 2 extremes, representing a unique system to study GPCR/ligand interactions. |
| 63 | 17123625 | In this review, we summarize the current knowledge of the structure-activity relationships in the TRH/TRH-R system. |
| 64 | 17123625 | Based on experimental data and the structural information acquired from computer simulations, we formulate a working hypothesis to describe the molecular events underlying the processes of TRH binding and TRH-R activation. |
| 65 | 17123625 | This hypothesis represents a starting point for understanding the biology of the TRH/TRH-R system on a molecular level and provides a basis for potential design of new potent and selective modulators of TRH-R's activity. |
| 66 | 17123625 | Thyrotropin-releasing hormone (TRH), a tripeptide, exerts its biological effects through stimulation of cell-surface receptors, TRH-R, belonging to the superfamily of G protein-coupled receptors (GPCR). |
| 67 | 17123625 | Because of the intermediate size of TRH, it is smaller than polypeptide ligands that interact at GPCR ectodomains and larger than biogenic amines, which interact within GPCR transmembrane domains (TMD), the TRH/TRH-R complex probably shares properties of these 2 extremes, representing a unique system to study GPCR/ligand interactions. |
| 68 | 17123625 | In this review, we summarize the current knowledge of the structure-activity relationships in the TRH/TRH-R system. |
| 69 | 17123625 | Based on experimental data and the structural information acquired from computer simulations, we formulate a working hypothesis to describe the molecular events underlying the processes of TRH binding and TRH-R activation. |
| 70 | 17123625 | This hypothesis represents a starting point for understanding the biology of the TRH/TRH-R system on a molecular level and provides a basis for potential design of new potent and selective modulators of TRH-R's activity. |
| 71 | 17465724 | Several GPCRs are involved in metabolic regulation and glucose homeostasis such as GLP-1 receptor, glucagon receptor, adiponectin receptor and so on. |
| 72 | 17465724 | GPR40 and GPR120 are activated by medium and long-chain FFAs, whereas GPR41 and GPR43 can be activated by short-chain FFAs. |
| 73 | 17465724 | GPR40, which is preferentially expressed in pancreatic beta-cells, mediates the majority of the effects of FFAs on insulin secretion. |
| 74 | 17992256 | Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. |
| 75 | 17992256 | This phenotype underscored the known importance of G(i/o) and hence of GPCRs for regulating insulin secretion. |
| 76 | 17992256 | We report that 3-iodothyronamine, a thyroid hormone metabolite, could negatively and positively regulate insulin secretion via the G(i)-coupled alpha(2A)-adrenergic receptor and the G(s)-coupled receptor Taar1, respectively, and protease-activated receptor-2 could negatively regulate insulin secretion and may contribute to physiological regulation of glucose metabolism. |
| 77 | 17992256 | Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. |
| 78 | 17992256 | This phenotype underscored the known importance of G(i/o) and hence of GPCRs for regulating insulin secretion. |
| 79 | 17992256 | We report that 3-iodothyronamine, a thyroid hormone metabolite, could negatively and positively regulate insulin secretion via the G(i)-coupled alpha(2A)-adrenergic receptor and the G(s)-coupled receptor Taar1, respectively, and protease-activated receptor-2 could negatively regulate insulin secretion and may contribute to physiological regulation of glucose metabolism. |
| 80 | 18248821 | Two examples of class B GPCRs that are involved in metabolic diseases are the Parathyroid hormone receptor 1 (PTHR1) and the Glucagon-like-peptide-1 receptor (GLP-1R) which play central roles in osteoporosis and diabetes mellitus type II, respectively. |
| 81 | 19076360 | PACAP binds to three types of G protein-coupled receptors (GPCRs): VPAC1 receptors, VPAC2 receptors, and PAC1 receptors. |
| 82 | 19076360 | PACAP stimulates insulin and glucagon secretion. |
| 83 | 19076360 | Deletion of PAC1 receptors or VPAC2 receptors results in impaired insulin secretion and glucose intolerance. |
| 84 | 19076360 | Studies in PAC1 receptor gene deleted mice have suggested that PACAP may be of physiological importance in mediating prandial insulin secretion and in contributing to the glucagon response to hypoglycemia. |
| 85 | 19126757 | While FXR(-/-) mice display both impaired glucose tolerance and decreased insulin sensitivity, activation of FXR improves hyperglycemia and dyslipidemia in vivo in diabetic mice. |
| 86 | 19126757 | Finally, a recent report also indicates that BA may regulate energy expenditure in a FXR-independent manner in mice, via activation of the G protein-coupled receptor TGR5. |
| 87 | 19365392 | This is evident from the recent success of glucagon-like peptide 1 (GLP1) mimetics and dipeptidyl peptidase 4 (DPP4) inhibitors, which promote activation of the GLP1 receptor to stimulate insulin secretion and inhibit glucagon secretion, and also have the potential to increase beta-cell mass. |
| 88 | 19365392 | Other islet beta-cell GPCRs that are involved in the regulation of islet function include the glucose-dependent insulinotropic peptide (GIP) receptor, lipid GPCRs, pleiotropic peptide GPCRs and islet biogenic amine GPCRs. |
| 89 | 19716570 | Some of these, including the induction of energy expenditure in brown adipose tissue and skeletal muscle as well as the stimulation of glucagon-like peptide-1 (GLP-1) production in enteroendocrine L-cells, are mediated by the G-protein-coupled bile acid receptor 1 (GPBAR1). |
| 90 | 19716570 | Therefore, we investigated in a cohort of white subjects at increased risk for type 2 diabetes mellitus whether a genetic variation within the GPBAR1 gene contributes to prediabetic phenotypes, such as disproportionate fat distribution, insulin resistance, or beta-cell dysfunction. |
| 91 | 19716570 | Some of these, including the induction of energy expenditure in brown adipose tissue and skeletal muscle as well as the stimulation of glucagon-like peptide-1 (GLP-1) production in enteroendocrine L-cells, are mediated by the G-protein-coupled bile acid receptor 1 (GPBAR1). |
| 92 | 19716570 | Therefore, we investigated in a cohort of white subjects at increased risk for type 2 diabetes mellitus whether a genetic variation within the GPBAR1 gene contributes to prediabetic phenotypes, such as disproportionate fat distribution, insulin resistance, or beta-cell dysfunction. |
| 93 | 19817802 | A novel islet GPCR is GPR54, which couples to the Gq isoform of G proteins, which in turn signal through the phospholipase C pathway. |
| 94 | 19817802 | Ligands for GPR54 are kisspeptins, which are peptides encoded in the KISS1 gene and also expressed in islet beta-cells. |
| 95 | 19911773 | This work revealed that betulinic (1), oleanolic (2), and ursolic acid (3) exhibited TGR5 agonist activity in a selective manner compared to bile acids, which also activated FXR, the nuclear bile acid receptor. |
| 96 | 19932133 | Primary bile acids (chenodeoxycholic acid and cholic acid) are physiological ligands/activators of farnesoid-X-receptor (FXR), pregnane-X-receptor (PXR) and constitutive androstane receptor (CAR), while litocholic acid is a ligand for the Vitamin D receptor (VDR) and the G-protein coupled receptor TGR5. |
| 97 | 19932133 | Despite FXR demonstrates a high selectivity for bile acids, PXR and CAR are relatively promiscuous receptors integrating lipid homeostasis with xenobiotic metabolism. |
| 98 | 19932133 | FXR, PXR, CAR and TGR exert synergistic activities in regulating lipid and glucose homeostasis and energy expenditure and liver and peripheral insulin sensitivity. |
| 99 | 20424139 | It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). |
| 100 | 20424139 | Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. |
| 101 | 20424139 | It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). |
| 102 | 20424139 | Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. |
| 103 | 20425070 | Recently, bile acids emerged as signaling molecules that, as ligands for the bile acid receptors farnesoid X receptor (FXR) and TGR5, activate and integrate multiple complex signaling pathways involved in lipid and glucose metabolism. |
| 104 | 20425070 | This article examines the mechanisms by which bile acid-mediated activation of FXR and TGR5 signaling pathways regulate lipid and glucose metabolism and the potential implications for bile acid sequestrant-mediated regulation of lipid and glucose levels in T2DM. |
| 105 | 20425070 | Recently, bile acids emerged as signaling molecules that, as ligands for the bile acid receptors farnesoid X receptor (FXR) and TGR5, activate and integrate multiple complex signaling pathways involved in lipid and glucose metabolism. |
| 106 | 20425070 | This article examines the mechanisms by which bile acid-mediated activation of FXR and TGR5 signaling pathways regulate lipid and glucose metabolism and the potential implications for bile acid sequestrant-mediated regulation of lipid and glucose levels in T2DM. |
| 107 | 20460915 | Additionally, they are ligands for a G-protein-coupled BA receptor (TGR5/Gpbar-1) and activate nuclear receptors such as farnesoid X receptor (FXR; NR1H4). |
| 108 | 20460915 | BA-activated FXR and signal transduction pathways are also involved in the regulation of hepatic gluconeogenesis, glycogen synthesis and insulin sensitivity. |
| 109 | 20460915 | Via TGR5, BA are able to stimulate glucagon-like peptide-1 secretion in the small intestine and energy expenditure in brown adipose tissue and skeletal muscle. |
| 110 | 20460915 | As such, FXR and/or TGR5 ligands have shown promising results in animal models of NAFLD and clinical pilot studies. |
| 111 | 20460915 | Despite being a poor FXR and TGR5 ligand, ursodeoxycholic acid (UDCA) improves hepatic ER stress and insulin sensitivity. |
| 112 | 20460915 | Additionally, they are ligands for a G-protein-coupled BA receptor (TGR5/Gpbar-1) and activate nuclear receptors such as farnesoid X receptor (FXR; NR1H4). |
| 113 | 20460915 | BA-activated FXR and signal transduction pathways are also involved in the regulation of hepatic gluconeogenesis, glycogen synthesis and insulin sensitivity. |
| 114 | 20460915 | Via TGR5, BA are able to stimulate glucagon-like peptide-1 secretion in the small intestine and energy expenditure in brown adipose tissue and skeletal muscle. |
| 115 | 20460915 | As such, FXR and/or TGR5 ligands have shown promising results in animal models of NAFLD and clinical pilot studies. |
| 116 | 20460915 | Despite being a poor FXR and TGR5 ligand, ursodeoxycholic acid (UDCA) improves hepatic ER stress and insulin sensitivity. |
| 117 | 20460915 | Additionally, they are ligands for a G-protein-coupled BA receptor (TGR5/Gpbar-1) and activate nuclear receptors such as farnesoid X receptor (FXR; NR1H4). |
| 118 | 20460915 | BA-activated FXR and signal transduction pathways are also involved in the regulation of hepatic gluconeogenesis, glycogen synthesis and insulin sensitivity. |
| 119 | 20460915 | Via TGR5, BA are able to stimulate glucagon-like peptide-1 secretion in the small intestine and energy expenditure in brown adipose tissue and skeletal muscle. |
| 120 | 20460915 | As such, FXR and/or TGR5 ligands have shown promising results in animal models of NAFLD and clinical pilot studies. |
| 121 | 20460915 | Despite being a poor FXR and TGR5 ligand, ursodeoxycholic acid (UDCA) improves hepatic ER stress and insulin sensitivity. |
| 122 | 20460915 | Additionally, they are ligands for a G-protein-coupled BA receptor (TGR5/Gpbar-1) and activate nuclear receptors such as farnesoid X receptor (FXR; NR1H4). |
| 123 | 20460915 | BA-activated FXR and signal transduction pathways are also involved in the regulation of hepatic gluconeogenesis, glycogen synthesis and insulin sensitivity. |
| 124 | 20460915 | Via TGR5, BA are able to stimulate glucagon-like peptide-1 secretion in the small intestine and energy expenditure in brown adipose tissue and skeletal muscle. |
| 125 | 20460915 | As such, FXR and/or TGR5 ligands have shown promising results in animal models of NAFLD and clinical pilot studies. |
| 126 | 20460915 | Despite being a poor FXR and TGR5 ligand, ursodeoxycholic acid (UDCA) improves hepatic ER stress and insulin sensitivity. |
| 127 | 21094903 | The glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor are homologous G-protein-coupled receptors (GPCRs). |
| 128 | 21431855 | The most prominent signaling molecules mediating bile acid signaling are the nuclear receptor farnesoid X receptor (FXR) and the membrane receptor TGR5. |
| 129 | 21649645 | The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. |
| 130 | 21649645 | In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. |
| 131 | 21649645 | The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. |
| 132 | 21649645 | This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. |
| 133 | 21649645 | The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. |
| 134 | 21649645 | In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. |
| 135 | 21649645 | The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. |
| 136 | 21649645 | This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. |
| 137 | 21649645 | The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. |
| 138 | 21649645 | In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. |
| 139 | 21649645 | The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. |
| 140 | 21649645 | This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. |
| 141 | 21663979 | Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases. |
| 142 | 21663979 | Free fatty acids (FFAs) have been demonstrated to act as ligands of several GPCRs including GPR40, GPR43, GPR84, GPR119 and GPR120. |
| 143 | 21663979 | We have recently shown that GPR120 acts as a physiological receptor of ω3 fatty acids in macrophages and adipocytes, which mediate potent anti-inflammatory and insulin sensitizing effects. |
| 144 | 21663979 | Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases. |
| 145 | 21663979 | Free fatty acids (FFAs) have been demonstrated to act as ligands of several GPCRs including GPR40, GPR43, GPR84, GPR119 and GPR120. |
| 146 | 21663979 | We have recently shown that GPR120 acts as a physiological receptor of ω3 fatty acids in macrophages and adipocytes, which mediate potent anti-inflammatory and insulin sensitizing effects. |
| 147 | 21722971 | Structural determination of several secretin family GPCR ECDs in complex with peptide ligands has been achieved recently, providing insight into the molecular determinants of hormone binding. |
| 148 | 21722971 | Recently, the first crystal structure of a RAMP ECD in complex with a secretin family GPCR was solved, revealing the elegant mechanism governing receptor selectivity of small molecule antagonists of the calcitonin gene-related peptide (CGRP) receptor. |
| 149 | 21722971 | Here we review the structural basis of ligand binding to secretin family GPCRs, concentrating on recent progress made on the structural basis of RAMP-modified GPCR pharmacology and its implications for rational drug design. |
| 150 | 21722971 | Structural determination of several secretin family GPCR ECDs in complex with peptide ligands has been achieved recently, providing insight into the molecular determinants of hormone binding. |
| 151 | 21722971 | Recently, the first crystal structure of a RAMP ECD in complex with a secretin family GPCR was solved, revealing the elegant mechanism governing receptor selectivity of small molecule antagonists of the calcitonin gene-related peptide (CGRP) receptor. |
| 152 | 21722971 | Here we review the structural basis of ligand binding to secretin family GPCRs, concentrating on recent progress made on the structural basis of RAMP-modified GPCR pharmacology and its implications for rational drug design. |
| 153 | 21722971 | Structural determination of several secretin family GPCR ECDs in complex with peptide ligands has been achieved recently, providing insight into the molecular determinants of hormone binding. |
| 154 | 21722971 | Recently, the first crystal structure of a RAMP ECD in complex with a secretin family GPCR was solved, revealing the elegant mechanism governing receptor selectivity of small molecule antagonists of the calcitonin gene-related peptide (CGRP) receptor. |
| 155 | 21722971 | Here we review the structural basis of ligand binding to secretin family GPCRs, concentrating on recent progress made on the structural basis of RAMP-modified GPCR pharmacology and its implications for rational drug design. |
| 156 | 21754919 | The expression of TGR5 and its function are distinct from the previously identified nuclear bile acid receptor, farnesoid X receptor (FXR). |
| 157 | 21754919 | The discovery of TGR5 expression in brown adipocyte tissues (BATs) and the recent demonstration of BAT in adult human body suggest a potential approach to combat obesity by targeting TGR5 to increase thermogenesis. |
| 158 | 21754919 | The expression of TGR5 and its function are distinct from the previously identified nuclear bile acid receptor, farnesoid X receptor (FXR). |
| 159 | 21754919 | The discovery of TGR5 expression in brown adipocyte tissues (BATs) and the recent demonstration of BAT in adult human body suggest a potential approach to combat obesity by targeting TGR5 to increase thermogenesis. |
| 160 | 21795304 | Proglucagon is cleaved to glucagon by prohormone convertase 2 (PC2) in pancreatic α-cells, but is cleaved to glucagon-like peptide-1 (GLP-1) by PC1 in intestinal L-cells. |
| 161 | 21795304 | The aim of this study was to identify mechanisms which switch processing of proglucagon to generate GLP-1 in the pancreas, given that GLP-1 can increase insulin secretion and β-cell mass. |
| 162 | 21795304 | The α-cell line, αTC1-6, expressed PC1 at low levels and GLP-1 was detected in cells and in culture media. |
| 163 | 21795304 | Three G protein-coupled receptors, GPR120, TGR5 and GPR119, implicated in the release of GLP-1 from L-cells are expressed in αTC1-6 cells. |
| 164 | 21795304 | Incubation of these cells with an agonist of TGR5 increased PC1 promoter activity and GLP-1 secretion suggesting that this is a mechanism for switching processing to GLP-1 in the pancreas. |
| 165 | 21795304 | Proglucagon is cleaved to glucagon by prohormone convertase 2 (PC2) in pancreatic α-cells, but is cleaved to glucagon-like peptide-1 (GLP-1) by PC1 in intestinal L-cells. |
| 166 | 21795304 | The aim of this study was to identify mechanisms which switch processing of proglucagon to generate GLP-1 in the pancreas, given that GLP-1 can increase insulin secretion and β-cell mass. |
| 167 | 21795304 | The α-cell line, αTC1-6, expressed PC1 at low levels and GLP-1 was detected in cells and in culture media. |
| 168 | 21795304 | Three G protein-coupled receptors, GPR120, TGR5 and GPR119, implicated in the release of GLP-1 from L-cells are expressed in αTC1-6 cells. |
| 169 | 21795304 | Incubation of these cells with an agonist of TGR5 increased PC1 promoter activity and GLP-1 secretion suggesting that this is a mechanism for switching processing to GLP-1 in the pancreas. |
| 170 | 22144677 | Bile acids also activate the farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5 and play a major role in regulating lipid, glucose, and energy metabolism. |
| 171 | 22144677 | Refeeding also induced CYP7A1 in fxr-deficient mice, indicating that FXR signaling did not play a role in postprandial regulation of bile acid synthesis. |
| 172 | 22144677 | In summary, this study demonstrates that glucose and insulin are major postprandial factors that induce CYP7A1 gene expression and bile acid synthesis. |
| 173 | 22266723 | Class B G-protein-coupled receptors (GPCRs) are receptors for peptide hormones that include glucagon, parathyroid hormone, and calcitonin. |
| 174 | 22521118 | Bile acid effects are mediated through the nuclear receptor farnesoid X receptor (FXR), the G-protein coupled receptor TGR5 (Gpbar-1) and various other bile acid sensing molecules. |
| 175 | 22521118 | Furthermore, activation of TGR5 promotes intestinal glucagon-like peptide-1 (GLP-1) release, thereby modulating glucose homeostasis and energy expenditure in brown adipose tissue and skeletal muscle. |
| 176 | 22521118 | Bile acid effects are mediated through the nuclear receptor farnesoid X receptor (FXR), the G-protein coupled receptor TGR5 (Gpbar-1) and various other bile acid sensing molecules. |
| 177 | 22521118 | Furthermore, activation of TGR5 promotes intestinal glucagon-like peptide-1 (GLP-1) release, thereby modulating glucose homeostasis and energy expenditure in brown adipose tissue and skeletal muscle. |
| 178 | 22550135 | The bile acid receptors farnesoid X receptor (FXR) and TGR5 both regulate lipid, glucose, and energy metabolism, rendering them potential pharmacological targets for MS therapy. |
| 179 | 22550135 | This review discusses the mechanisms of metabolic regulation by FXR and TGR5 and the utility relevance of natural and synthetic modulators of FXR and TGR5 activity, including bile acid sequestrants, in the treatment of the MS. |
| 180 | 22550135 | The bile acid receptors farnesoid X receptor (FXR) and TGR5 both regulate lipid, glucose, and energy metabolism, rendering them potential pharmacological targets for MS therapy. |
| 181 | 22550135 | This review discusses the mechanisms of metabolic regulation by FXR and TGR5 and the utility relevance of natural and synthetic modulators of FXR and TGR5 activity, including bile acid sequestrants, in the treatment of the MS. |
| 182 | 22649424 | In contrast to the larger and more thoroughly studied GPCR subfamilies A and C, the B1 subfamily is small and comprises only 15 members, including, e.g., the secretin receptor, the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). |
| 183 | 22659620 | The G protein-coupled receptors (GPCRs) for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon are emerging as targets to treat both hyperglycemia and obesity. |
| 184 | 22659620 | GIP is rapidly released from intestinal K-cells following food intake and stimulates glucose-dependent insulin secretion from β-cells and the storage of fat in adipocytes. |
| 185 | 22659620 | Both GIP receptor agonists and antagonists have been demonstrated to display therapeutic potential to treat diabetes and obesity. |
| 186 | 22659620 | Similar to GIP, GLP-1 is released from intestinal L-cells following food intake and potentiates glucose-dependent insulin secretion from β-cells. |
| 187 | 22659620 | Here we review the biology of GIP, GLP-1 and glucagon and examine the various therapeutic strategies to activate and antagonize the receptors of these peptides. |
| 188 | 22708876 | It is selective for glucagon receptor relative to other family B GPCRs, showing IC(50) values of 1020 nM for GIPR, 9200 nM for PAC1, and >10000 nM for GLP-1R, VPAC1, and VPAC2. |
| 189 | 22745195 | Because of structural homology among GPCR, clarification of the role of ICL1 in PROKR2 activity may contribute to a better understanding of this domain across other GPCR. |
| 190 | 22860017 | Full-length RAGE, a cell surface-located type I membrane protein, can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble RAGE form. |
| 191 | 22860017 | We chose three different GPCRs coupled to distinct signaling cascades: the V2 vasopressin receptor (V2R) activating adenylyl cyclase, the oxytocin receptor (OTR) linked to phospholipase Cβ, and the PACAP receptor (subtype PAC1) coupled to adenylyl cyclase, phospholipase Cβ, calcium signaling and MAP kinases. |
| 192 | 22860017 | We generated HEK cell lines stably coexpressing an individual GPCR and full-length RAGE and then investigated GPCR ligand-induced activation of RAGE shedding. |
| 193 | 22860017 | By using specific inhibitors we have identified Ca(2+) signaling, PKCα/PKCβI, CaMKII, PI3 kinases and MAP kinases to be involved in PAC1 receptor-induced RAGE shedding. |
| 194 | 22860017 | Furthermore, by using a selective metalloproteinase inhibitor and siRNA-mediated knock-down approaches, we show that ADAM10 and/or MMP9 are playing important roles in constitutive and PACAP-induced RAGE shedding. |
| 195 | 22860017 | Full-length RAGE, a cell surface-located type I membrane protein, can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble RAGE form. |
| 196 | 22860017 | We chose three different GPCRs coupled to distinct signaling cascades: the V2 vasopressin receptor (V2R) activating adenylyl cyclase, the oxytocin receptor (OTR) linked to phospholipase Cβ, and the PACAP receptor (subtype PAC1) coupled to adenylyl cyclase, phospholipase Cβ, calcium signaling and MAP kinases. |
| 197 | 22860017 | We generated HEK cell lines stably coexpressing an individual GPCR and full-length RAGE and then investigated GPCR ligand-induced activation of RAGE shedding. |
| 198 | 22860017 | By using specific inhibitors we have identified Ca(2+) signaling, PKCα/PKCβI, CaMKII, PI3 kinases and MAP kinases to be involved in PAC1 receptor-induced RAGE shedding. |
| 199 | 22860017 | Furthermore, by using a selective metalloproteinase inhibitor and siRNA-mediated knock-down approaches, we show that ADAM10 and/or MMP9 are playing important roles in constitutive and PACAP-induced RAGE shedding. |
| 200 | 23162538 | The VPAC1 receptor: structure and function of a class B GPCR prototype. |
| 201 | 23162538 | The VPAC1 receptor which is an archetype of the class B GPCRs binds Vasoactive Intestinal Peptide (VIP), a neuropeptide widely distributed in central and peripheral nervous system modulating many physiological processes including regulation of exocrine secretions, hormone release, foetal development, immune response … VIP appears to exert beneficial effect in neurodegenerative and inflammatory diseases. |
| 202 | 23162538 | The VPAC1 receptor: structure and function of a class B GPCR prototype. |
| 203 | 23162538 | The VPAC1 receptor which is an archetype of the class B GPCRs binds Vasoactive Intestinal Peptide (VIP), a neuropeptide widely distributed in central and peripheral nervous system modulating many physiological processes including regulation of exocrine secretions, hormone release, foetal development, immune response … VIP appears to exert beneficial effect in neurodegenerative and inflammatory diseases. |
| 204 | 23179047 | Pharmacological receptor binding studies on these GPCR ligand-derivatized AuNPs (2-5 nm in diameter), performed using membranes of mammalian cells stably expressing human A1, A2A, and A3ARs, showed that the desired selectivity was retained with K(i) values (nanomolar) of A3AR agonist 21b and A2AAR antagonists 24 and 26a of 14 (A3), 34 (A2A), and 69 (A2A), respectively. |
| 205 | 23293632 | One such GPCR is the bombesin receptor subtype 3 (BRS-3). |
| 206 | 23293632 | Two Drosophila GPCRs (CG30106 and CG14593) belong to the BRS-3 phylogenetic subgroup. |
| 207 | 23293632 | One such GPCR is the bombesin receptor subtype 3 (BRS-3). |
| 208 | 23293632 | Two Drosophila GPCRs (CG30106 and CG14593) belong to the BRS-3 phylogenetic subgroup. |
| 209 | 23420103 | Two key BA receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), were recently identified, which provides great insights into BAs' normal physiological functions as well as their carcinogenic effects. |
| 210 | 23420103 | FXR and TGR5 not only play key roles in regulating BA homeostasis but also are essential in suppressing BAs' carcinogenic effects on liver cancer. |
| 211 | 23420103 | Two key BA receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), were recently identified, which provides great insights into BAs' normal physiological functions as well as their carcinogenic effects. |
| 212 | 23420103 | FXR and TGR5 not only play key roles in regulating BA homeostasis but also are essential in suppressing BAs' carcinogenic effects on liver cancer. |
| 213 | 23583575 | GPCR signalling is well known to proceed through several linear pathways involving activation of G proteins and their downstream signalling pathways such as activation of phospholipase C. |
| 214 | 23583575 | In addition, GPCRs signal via transactivation of Protein Tyrosine Kinase receptors such as that for Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) where GPCR agonists mediate increase levels of phosphorylated Erk (pErk) the immediate downstream product of the activation of EGF receptor. |
| 215 | 23583575 | It has recently been shown that this paradigm can be extended to include the GPCR transactivation of a Protein Serine/Threonine Kinase receptor, specifically the Transforming Growth Factor β Type I receptor (also known as Alk V) (TβRI) in which case GPCR activation leads to the formation of carboxy terminal polyphosphorylated Smad2 (phosphoSmad2) being the immediate downstream product of the activation of TβRI. |
| 216 | 23583575 | In the example of proteoglycan synthesis stimulated by GPCR agonists such as thrombin and endothelin-1, the transactivation pathways for the EGF receptor and TβRI are both active and together account for essentially all of the response to the GPCRs. |
| 217 | 23583575 | In contrast, signalling downstream of GPCRs such as increased inositol 1,4,5 trisphosphate (IP3) and intracellular calcium do not have any effect on GPCR stimulated proteoglycan synthesis. |
| 218 | 23583575 | GPCR signalling is well known to proceed through several linear pathways involving activation of G proteins and their downstream signalling pathways such as activation of phospholipase C. |
| 219 | 23583575 | In addition, GPCRs signal via transactivation of Protein Tyrosine Kinase receptors such as that for Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) where GPCR agonists mediate increase levels of phosphorylated Erk (pErk) the immediate downstream product of the activation of EGF receptor. |
| 220 | 23583575 | It has recently been shown that this paradigm can be extended to include the GPCR transactivation of a Protein Serine/Threonine Kinase receptor, specifically the Transforming Growth Factor β Type I receptor (also known as Alk V) (TβRI) in which case GPCR activation leads to the formation of carboxy terminal polyphosphorylated Smad2 (phosphoSmad2) being the immediate downstream product of the activation of TβRI. |
| 221 | 23583575 | In the example of proteoglycan synthesis stimulated by GPCR agonists such as thrombin and endothelin-1, the transactivation pathways for the EGF receptor and TβRI are both active and together account for essentially all of the response to the GPCRs. |
| 222 | 23583575 | In contrast, signalling downstream of GPCRs such as increased inositol 1,4,5 trisphosphate (IP3) and intracellular calcium do not have any effect on GPCR stimulated proteoglycan synthesis. |
| 223 | 23583575 | GPCR signalling is well known to proceed through several linear pathways involving activation of G proteins and their downstream signalling pathways such as activation of phospholipase C. |
| 224 | 23583575 | In addition, GPCRs signal via transactivation of Protein Tyrosine Kinase receptors such as that for Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) where GPCR agonists mediate increase levels of phosphorylated Erk (pErk) the immediate downstream product of the activation of EGF receptor. |
| 225 | 23583575 | It has recently been shown that this paradigm can be extended to include the GPCR transactivation of a Protein Serine/Threonine Kinase receptor, specifically the Transforming Growth Factor β Type I receptor (also known as Alk V) (TβRI) in which case GPCR activation leads to the formation of carboxy terminal polyphosphorylated Smad2 (phosphoSmad2) being the immediate downstream product of the activation of TβRI. |
| 226 | 23583575 | In the example of proteoglycan synthesis stimulated by GPCR agonists such as thrombin and endothelin-1, the transactivation pathways for the EGF receptor and TβRI are both active and together account for essentially all of the response to the GPCRs. |
| 227 | 23583575 | In contrast, signalling downstream of GPCRs such as increased inositol 1,4,5 trisphosphate (IP3) and intracellular calcium do not have any effect on GPCR stimulated proteoglycan synthesis. |
| 228 | 23583575 | GPCR signalling is well known to proceed through several linear pathways involving activation of G proteins and their downstream signalling pathways such as activation of phospholipase C. |
| 229 | 23583575 | In addition, GPCRs signal via transactivation of Protein Tyrosine Kinase receptors such as that for Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) where GPCR agonists mediate increase levels of phosphorylated Erk (pErk) the immediate downstream product of the activation of EGF receptor. |
| 230 | 23583575 | It has recently been shown that this paradigm can be extended to include the GPCR transactivation of a Protein Serine/Threonine Kinase receptor, specifically the Transforming Growth Factor β Type I receptor (also known as Alk V) (TβRI) in which case GPCR activation leads to the formation of carboxy terminal polyphosphorylated Smad2 (phosphoSmad2) being the immediate downstream product of the activation of TβRI. |
| 231 | 23583575 | In the example of proteoglycan synthesis stimulated by GPCR agonists such as thrombin and endothelin-1, the transactivation pathways for the EGF receptor and TβRI are both active and together account for essentially all of the response to the GPCRs. |
| 232 | 23583575 | In contrast, signalling downstream of GPCRs such as increased inositol 1,4,5 trisphosphate (IP3) and intracellular calcium do not have any effect on GPCR stimulated proteoglycan synthesis. |
| 233 | 23583575 | GPCR signalling is well known to proceed through several linear pathways involving activation of G proteins and their downstream signalling pathways such as activation of phospholipase C. |
| 234 | 23583575 | In addition, GPCRs signal via transactivation of Protein Tyrosine Kinase receptors such as that for Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) where GPCR agonists mediate increase levels of phosphorylated Erk (pErk) the immediate downstream product of the activation of EGF receptor. |
| 235 | 23583575 | It has recently been shown that this paradigm can be extended to include the GPCR transactivation of a Protein Serine/Threonine Kinase receptor, specifically the Transforming Growth Factor β Type I receptor (also known as Alk V) (TβRI) in which case GPCR activation leads to the formation of carboxy terminal polyphosphorylated Smad2 (phosphoSmad2) being the immediate downstream product of the activation of TβRI. |
| 236 | 23583575 | In the example of proteoglycan synthesis stimulated by GPCR agonists such as thrombin and endothelin-1, the transactivation pathways for the EGF receptor and TβRI are both active and together account for essentially all of the response to the GPCRs. |
| 237 | 23583575 | In contrast, signalling downstream of GPCRs such as increased inositol 1,4,5 trisphosphate (IP3) and intracellular calcium do not have any effect on GPCR stimulated proteoglycan synthesis. |
| 238 | 23597780 | Glucagon exerts its action by binding to its receptor, glucagon receptor (GCGR), one of class B G-protein coupled receptors (GPCRs). |
| 239 | 23694765 | G-protein coupled receptors (GPCRs) regulate hormone secretion from islets of Langerhans, and recently developed therapies for type-2 diabetes target islet GLP-1 receptors. |
| 240 | 23694765 | We have used this atlas to describe how islet GPCRs interact with their endogenous ligands, regulate islet hormone secretion, and interact with drugs known to target GPCRs, with a focus on drug/receptor interactions that may affect insulin secretion. |
| 241 | 23694765 | The islet GPCRome consists of 293 GPCRs, a majority of which have unknown effects on insulin, glucagon and somatostatin secretion. |
| 242 | 23694765 | Islet GPCRs are also the targets of a large number of clinically used drugs, and based on their coupling characteristics and effects on receptor signalling we identified 107 drugs predicted to stimulate and 184 drugs predicted to inhibit insulin secretion. |
| 243 | 23694765 | The islet GPCRome highlights knowledge gaps in the current understanding of islet GPCR function, and identifies GPCR/ligand/drug interactions that might affect insulin secretion, which are important for understanding the metabolic side effects of drugs. |
| 244 | 23694765 | G-protein coupled receptors (GPCRs) regulate hormone secretion from islets of Langerhans, and recently developed therapies for type-2 diabetes target islet GLP-1 receptors. |
| 245 | 23694765 | We have used this atlas to describe how islet GPCRs interact with their endogenous ligands, regulate islet hormone secretion, and interact with drugs known to target GPCRs, with a focus on drug/receptor interactions that may affect insulin secretion. |
| 246 | 23694765 | The islet GPCRome consists of 293 GPCRs, a majority of which have unknown effects on insulin, glucagon and somatostatin secretion. |
| 247 | 23694765 | Islet GPCRs are also the targets of a large number of clinically used drugs, and based on their coupling characteristics and effects on receptor signalling we identified 107 drugs predicted to stimulate and 184 drugs predicted to inhibit insulin secretion. |
| 248 | 23694765 | The islet GPCRome highlights knowledge gaps in the current understanding of islet GPCR function, and identifies GPCR/ligand/drug interactions that might affect insulin secretion, which are important for understanding the metabolic side effects of drugs. |
| 249 | 23694765 | G-protein coupled receptors (GPCRs) regulate hormone secretion from islets of Langerhans, and recently developed therapies for type-2 diabetes target islet GLP-1 receptors. |
| 250 | 23694765 | We have used this atlas to describe how islet GPCRs interact with their endogenous ligands, regulate islet hormone secretion, and interact with drugs known to target GPCRs, with a focus on drug/receptor interactions that may affect insulin secretion. |
| 251 | 23694765 | The islet GPCRome consists of 293 GPCRs, a majority of which have unknown effects on insulin, glucagon and somatostatin secretion. |
| 252 | 23694765 | Islet GPCRs are also the targets of a large number of clinically used drugs, and based on their coupling characteristics and effects on receptor signalling we identified 107 drugs predicted to stimulate and 184 drugs predicted to inhibit insulin secretion. |
| 253 | 23694765 | The islet GPCRome highlights knowledge gaps in the current understanding of islet GPCR function, and identifies GPCR/ligand/drug interactions that might affect insulin secretion, which are important for understanding the metabolic side effects of drugs. |
| 254 | 23694765 | G-protein coupled receptors (GPCRs) regulate hormone secretion from islets of Langerhans, and recently developed therapies for type-2 diabetes target islet GLP-1 receptors. |
| 255 | 23694765 | We have used this atlas to describe how islet GPCRs interact with their endogenous ligands, regulate islet hormone secretion, and interact with drugs known to target GPCRs, with a focus on drug/receptor interactions that may affect insulin secretion. |
| 256 | 23694765 | The islet GPCRome consists of 293 GPCRs, a majority of which have unknown effects on insulin, glucagon and somatostatin secretion. |
| 257 | 23694765 | Islet GPCRs are also the targets of a large number of clinically used drugs, and based on their coupling characteristics and effects on receptor signalling we identified 107 drugs predicted to stimulate and 184 drugs predicted to inhibit insulin secretion. |
| 258 | 23694765 | The islet GPCRome highlights knowledge gaps in the current understanding of islet GPCR function, and identifies GPCR/ligand/drug interactions that might affect insulin secretion, which are important for understanding the metabolic side effects of drugs. |
| 259 | 23694765 | G-protein coupled receptors (GPCRs) regulate hormone secretion from islets of Langerhans, and recently developed therapies for type-2 diabetes target islet GLP-1 receptors. |
| 260 | 23694765 | We have used this atlas to describe how islet GPCRs interact with their endogenous ligands, regulate islet hormone secretion, and interact with drugs known to target GPCRs, with a focus on drug/receptor interactions that may affect insulin secretion. |
| 261 | 23694765 | The islet GPCRome consists of 293 GPCRs, a majority of which have unknown effects on insulin, glucagon and somatostatin secretion. |
| 262 | 23694765 | Islet GPCRs are also the targets of a large number of clinically used drugs, and based on their coupling characteristics and effects on receptor signalling we identified 107 drugs predicted to stimulate and 184 drugs predicted to inhibit insulin secretion. |
| 263 | 23694765 | The islet GPCRome highlights knowledge gaps in the current understanding of islet GPCR function, and identifies GPCR/ligand/drug interactions that might affect insulin secretion, which are important for understanding the metabolic side effects of drugs. |
| 264 | 23729782 | Recent discoveries show that bile acids also function as signaling molecules that exert diverse endocrine and metabolic actions by activating G protein-coupled bile acid receptor 1 (GPBAR1/G-protein-coupled bile acid receptor 1 or TGR5), a membrane G protein-coupled receptor, and farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily. |
| 265 | 23729782 | These bile acid sensing receptors are expressed in intestinal epithelial cells, TGR5 in enteroendocrine cells and FXR in enterocytes, which line the mucosa of gut lumen. |
| 266 | 23729782 | The biological actions induced by bile acid activation of intestinal FXR and TGR5 have important therapeutic implications for the pathogenesis and treatment of several metabolic diseases, such as cholestasis and diabetes. |
| 267 | 23729782 | Recent discoveries show that bile acids also function as signaling molecules that exert diverse endocrine and metabolic actions by activating G protein-coupled bile acid receptor 1 (GPBAR1/G-protein-coupled bile acid receptor 1 or TGR5), a membrane G protein-coupled receptor, and farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily. |
| 268 | 23729782 | These bile acid sensing receptors are expressed in intestinal epithelial cells, TGR5 in enteroendocrine cells and FXR in enterocytes, which line the mucosa of gut lumen. |
| 269 | 23729782 | The biological actions induced by bile acid activation of intestinal FXR and TGR5 have important therapeutic implications for the pathogenesis and treatment of several metabolic diseases, such as cholestasis and diabetes. |
| 270 | 23729782 | Recent discoveries show that bile acids also function as signaling molecules that exert diverse endocrine and metabolic actions by activating G protein-coupled bile acid receptor 1 (GPBAR1/G-protein-coupled bile acid receptor 1 or TGR5), a membrane G protein-coupled receptor, and farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily. |
| 271 | 23729782 | These bile acid sensing receptors are expressed in intestinal epithelial cells, TGR5 in enteroendocrine cells and FXR in enterocytes, which line the mucosa of gut lumen. |
| 272 | 23729782 | The biological actions induced by bile acid activation of intestinal FXR and TGR5 have important therapeutic implications for the pathogenesis and treatment of several metabolic diseases, such as cholestasis and diabetes. |
| 273 | 23782454 | TGR5 ligands improve insulin sensitivity and glucose homeostasis through the secretion of incretins. |
| 274 | 23784309 | These signaling pathways involve the activation of the nuclear receptor farnesoid X receptor (FXRα) or of the G protein-coupled receptor TGR5. |
| 275 | 23909843 | While SFAs have been shown to induce inflammation, PUFAs have anti-inflammatory effects by downregulating NF-kappaB, IL-1β, TNF-α and IL-6 despite upregulating of IL-10. |
| 276 | 23909843 | It is suggested that FFA may activate Toll Like Receptor-4 (TLR4) and G protein-coupled receptors (GPCR) activating signaling pathways that promote production and release of inflammatory cytokines (IL-6 and TFN-α). |
| 277 | 23909843 | Fatty acid action on TLR4, peroxisome proliferator-activated receptors (PPARs) and GPCRs are potential therapeutic targets for controlling FFA-induced inflammation. |
| 278 | 23909843 | While SFAs have been shown to induce inflammation, PUFAs have anti-inflammatory effects by downregulating NF-kappaB, IL-1β, TNF-α and IL-6 despite upregulating of IL-10. |
| 279 | 23909843 | It is suggested that FFA may activate Toll Like Receptor-4 (TLR4) and G protein-coupled receptors (GPCR) activating signaling pathways that promote production and release of inflammatory cytokines (IL-6 and TFN-α). |
| 280 | 23909843 | Fatty acid action on TLR4, peroxisome proliferator-activated receptors (PPARs) and GPCRs are potential therapeutic targets for controlling FFA-induced inflammation. |
| 281 | 20631053 | Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. |
| 282 | 20631053 | Two dedicated receptors for bile acids (BAs) have been identified, the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, which represent attractive targets for the treatment of metabolic and chronic liver diseases. |
| 283 | 20631053 | Previous work characterized 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (INT-747), a potent and selective FXR agonist, as well as 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (INT-777), a potent and selective TGR5 agonist. |
| 284 | 20631053 | INT-767 is a potent agonist for both FXR (mean EC(50), 30 nM by PerkinElmer AlphaScreen assay) and TGR5 (mean EC(50), 630 nM by time resolved-fluorescence resonance energy transfer), the first compound described so far to potently and selectively activate both BA receptors. |
| 285 | 20631053 | INT-767 does not show cytotoxic effects in HepG2 cells, does not inhibit cytochrome P450 enzymes, is highly stable to phase I and II enzymatic modifications, and does not inhibit the human ether-a-go-go-related gene potassium channel. |
| 286 | 20631053 | In line with its dual activity, INT-767 induces FXR-dependent lipid uptake by adipocytes, with the beneficial effect of shuttling lipids from central hepatic to peripheral fat storage, and promotes TGR5-dependent glucagon-like peptide-1 secretion by enteroendocrine cells, a validated target in the treatment of type 2 diabetes. |
| 287 | 20631053 | Collectively, these preclinical results indicate that INT-767 is a safe and effective modulator of FXR and TGR5-dependent pathways, suggesting potential clinical applications in the treatment of liver and metabolic diseases. |
| 288 | 20631053 | Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. |
| 289 | 20631053 | Two dedicated receptors for bile acids (BAs) have been identified, the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, which represent attractive targets for the treatment of metabolic and chronic liver diseases. |
| 290 | 20631053 | Previous work characterized 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (INT-747), a potent and selective FXR agonist, as well as 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (INT-777), a potent and selective TGR5 agonist. |
| 291 | 20631053 | INT-767 is a potent agonist for both FXR (mean EC(50), 30 nM by PerkinElmer AlphaScreen assay) and TGR5 (mean EC(50), 630 nM by time resolved-fluorescence resonance energy transfer), the first compound described so far to potently and selectively activate both BA receptors. |
| 292 | 20631053 | INT-767 does not show cytotoxic effects in HepG2 cells, does not inhibit cytochrome P450 enzymes, is highly stable to phase I and II enzymatic modifications, and does not inhibit the human ether-a-go-go-related gene potassium channel. |
| 293 | 20631053 | In line with its dual activity, INT-767 induces FXR-dependent lipid uptake by adipocytes, with the beneficial effect of shuttling lipids from central hepatic to peripheral fat storage, and promotes TGR5-dependent glucagon-like peptide-1 secretion by enteroendocrine cells, a validated target in the treatment of type 2 diabetes. |
| 294 | 20631053 | Collectively, these preclinical results indicate that INT-767 is a safe and effective modulator of FXR and TGR5-dependent pathways, suggesting potential clinical applications in the treatment of liver and metabolic diseases. |
| 295 | 20631053 | Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. |
| 296 | 20631053 | Two dedicated receptors for bile acids (BAs) have been identified, the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, which represent attractive targets for the treatment of metabolic and chronic liver diseases. |
| 297 | 20631053 | Previous work characterized 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (INT-747), a potent and selective FXR agonist, as well as 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (INT-777), a potent and selective TGR5 agonist. |
| 298 | 20631053 | INT-767 is a potent agonist for both FXR (mean EC(50), 30 nM by PerkinElmer AlphaScreen assay) and TGR5 (mean EC(50), 630 nM by time resolved-fluorescence resonance energy transfer), the first compound described so far to potently and selectively activate both BA receptors. |
| 299 | 20631053 | INT-767 does not show cytotoxic effects in HepG2 cells, does not inhibit cytochrome P450 enzymes, is highly stable to phase I and II enzymatic modifications, and does not inhibit the human ether-a-go-go-related gene potassium channel. |
| 300 | 20631053 | In line with its dual activity, INT-767 induces FXR-dependent lipid uptake by adipocytes, with the beneficial effect of shuttling lipids from central hepatic to peripheral fat storage, and promotes TGR5-dependent glucagon-like peptide-1 secretion by enteroendocrine cells, a validated target in the treatment of type 2 diabetes. |
| 301 | 20631053 | Collectively, these preclinical results indicate that INT-767 is a safe and effective modulator of FXR and TGR5-dependent pathways, suggesting potential clinical applications in the treatment of liver and metabolic diseases. |
| 302 | 20631053 | Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. |
| 303 | 20631053 | Two dedicated receptors for bile acids (BAs) have been identified, the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, which represent attractive targets for the treatment of metabolic and chronic liver diseases. |
| 304 | 20631053 | Previous work characterized 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (INT-747), a potent and selective FXR agonist, as well as 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (INT-777), a potent and selective TGR5 agonist. |
| 305 | 20631053 | INT-767 is a potent agonist for both FXR (mean EC(50), 30 nM by PerkinElmer AlphaScreen assay) and TGR5 (mean EC(50), 630 nM by time resolved-fluorescence resonance energy transfer), the first compound described so far to potently and selectively activate both BA receptors. |
| 306 | 20631053 | INT-767 does not show cytotoxic effects in HepG2 cells, does not inhibit cytochrome P450 enzymes, is highly stable to phase I and II enzymatic modifications, and does not inhibit the human ether-a-go-go-related gene potassium channel. |
| 307 | 20631053 | In line with its dual activity, INT-767 induces FXR-dependent lipid uptake by adipocytes, with the beneficial effect of shuttling lipids from central hepatic to peripheral fat storage, and promotes TGR5-dependent glucagon-like peptide-1 secretion by enteroendocrine cells, a validated target in the treatment of type 2 diabetes. |
| 308 | 20631053 | Collectively, these preclinical results indicate that INT-767 is a safe and effective modulator of FXR and TGR5-dependent pathways, suggesting potential clinical applications in the treatment of liver and metabolic diseases. |
| 309 | 20631053 | Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. |
| 310 | 20631053 | Two dedicated receptors for bile acids (BAs) have been identified, the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, which represent attractive targets for the treatment of metabolic and chronic liver diseases. |
| 311 | 20631053 | Previous work characterized 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (INT-747), a potent and selective FXR agonist, as well as 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (INT-777), a potent and selective TGR5 agonist. |
| 312 | 20631053 | INT-767 is a potent agonist for both FXR (mean EC(50), 30 nM by PerkinElmer AlphaScreen assay) and TGR5 (mean EC(50), 630 nM by time resolved-fluorescence resonance energy transfer), the first compound described so far to potently and selectively activate both BA receptors. |
| 313 | 20631053 | INT-767 does not show cytotoxic effects in HepG2 cells, does not inhibit cytochrome P450 enzymes, is highly stable to phase I and II enzymatic modifications, and does not inhibit the human ether-a-go-go-related gene potassium channel. |
| 314 | 20631053 | In line with its dual activity, INT-767 induces FXR-dependent lipid uptake by adipocytes, with the beneficial effect of shuttling lipids from central hepatic to peripheral fat storage, and promotes TGR5-dependent glucagon-like peptide-1 secretion by enteroendocrine cells, a validated target in the treatment of type 2 diabetes. |
| 315 | 20631053 | Collectively, these preclinical results indicate that INT-767 is a safe and effective modulator of FXR and TGR5-dependent pathways, suggesting potential clinical applications in the treatment of liver and metabolic diseases. |
| 316 | 20631053 | Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. |
| 317 | 20631053 | Two dedicated receptors for bile acids (BAs) have been identified, the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, which represent attractive targets for the treatment of metabolic and chronic liver diseases. |
| 318 | 20631053 | Previous work characterized 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (INT-747), a potent and selective FXR agonist, as well as 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (INT-777), a potent and selective TGR5 agonist. |
| 319 | 20631053 | INT-767 is a potent agonist for both FXR (mean EC(50), 30 nM by PerkinElmer AlphaScreen assay) and TGR5 (mean EC(50), 630 nM by time resolved-fluorescence resonance energy transfer), the first compound described so far to potently and selectively activate both BA receptors. |
| 320 | 20631053 | INT-767 does not show cytotoxic effects in HepG2 cells, does not inhibit cytochrome P450 enzymes, is highly stable to phase I and II enzymatic modifications, and does not inhibit the human ether-a-go-go-related gene potassium channel. |
| 321 | 20631053 | In line with its dual activity, INT-767 induces FXR-dependent lipid uptake by adipocytes, with the beneficial effect of shuttling lipids from central hepatic to peripheral fat storage, and promotes TGR5-dependent glucagon-like peptide-1 secretion by enteroendocrine cells, a validated target in the treatment of type 2 diabetes. |
| 322 | 20631053 | Collectively, these preclinical results indicate that INT-767 is a safe and effective modulator of FXR and TGR5-dependent pathways, suggesting potential clinical applications in the treatment of liver and metabolic diseases. |